JPH1129588A - Production of diphenylphosphoryl azide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject compound having high quality easily, safely and quantitatively stably by dissolving diphenylphosphoryl chloride in a specific solvent and reacting the solution with an aqueous sodium azide solution in the presence of a specific catalyst. SOLUTION: (C) Diphenylphosphoryl azide of formula II is obtained by reacting (A) a diphenylphosphoryl chloride of formula I with (B) an aqueous solution of an inorganic azide salt of the formula, M(N3 )n [M is an alkali metal or alkaline earth metal; (n) is 1 or 2] in the presence of a phase transfer catalyst (e.g. a quaternary ammonium salt of tetra-n-butylammonium bromide, etc.) in a water immiscible inactive solvent (preferably cyclohexane, toluene, etc.). The used amount of the ingredient B is 1.0-3.0 mole, preferably 1.0-1.1 mole calculated in terms of hydrogen azide for 1 mole of the ingredient A.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel method for producing diphenylphosphoryl azide using diphenylphosphoryl chloride as a raw material. Diphenylphosphoryl azide is a useful dehydrating condensing agent in the production of pharmaceuticals and the like, and is also useful as an aminating agent and the like.

[0002]

2. Description of the Related Art Conventionally, a method for synthesizing diphenylphosphoryl azide is to react diphenylphosphoryl chloride with sodium azide in the presence of an acetone solvent or a mixed solvent of acetone-water without a catalyst. Only the method is known.

[0003] For example, in JP-A-48-80545, acetone is used as a reaction solvent, and sodium azide and diphenylphosphoryl chloride are reacted at room temperature to obtain a yield of 92%. Also, J.I. Org. Che
m. , 57 (1992) 23, 6294-6300, a reaction of diphenylphosphoryl chloride and sodium azide in a mixed solvent system of acetone and water to obtain a yield of 90%.

However, these methods have the following problems and cannot be said to be suitable for industrial production. (1) Even if the synthesis is performed under the same conditions, there are cases where the reaction is completed quickly and cases where the conversion reaction does not proceed at all during the course, and there is no quantitative stability of the reaction. (2) To complete the reaction, an excess of sodium azide insoluble in acetone is required.
Additional examination of Example 1 described in Japanese Patent Publication No. 45 shows that by the completion of the reaction, 5 equivalents of sodium azide had to be added in several portions, although it was theoretically 1 equivalent to diphenylphosphoryl chloride. . In addition, the sodium chloride cake contaminated with this excess sodium azide must be worked up. (3) The quality between lots is not stable in coloring and purity.

The present invention solves the above-mentioned problems and provides a method for producing high-quality diphenylphosphoryl azide easily, safely and with excellent quantitative stability.

[0006]

Means for Solving the Problems The present inventors have intensively studied an industrially advantageous method for achieving the above object, and found that diphenylphosphoryl chloride was dissolved in a non-water-miscible inert solvent. Then, in the presence of an anion mobile phase transfer catalyst, a method for converting into azide by reaction with aqueous sodium azide was found, and the present invention was completed.

That is, the present invention provides a method of mixing a diphenylphosphoryl chloride of the formula (1) with an aqueous solution of an inorganic azide salt represented by the general formula (2) in the presence of a phase transfer catalyst useful for anion transfer. A method for producing diphenylphosphoryl azide represented by the formula (3), characterized in that the reaction is carried out in an inert solvent.

Embedded image (1) M (N ₃ ) n (2) (wherein, M is an alkali metal or an alkaline earth metal, and n is 1 or 2)

Embedded image (3)

This new method using a phase transfer catalyst is
This is a method for synthesizing diphenylphosphoryl azide having excellent quantitative stability of the reaction.

Further, since the driving force of the two-molecule reaction is given by the phase transfer reaction, the reaction is completed with a much smaller amount of sodium azide than in the prior art. Thus, the reaction time is significantly shorter than required by conventional methods, and the operability in the process is improved.

[0010] In addition, since the conventional method uses acetone which is an aqueous solvent, if it is intended to remove impurities such as hydrolyzate contained in the produced diphenylphosphoryl azide by washing with water, diphenylphosphoryl azide may be used. Azide itself undergoes hydrolysis, and no effective cleaning method has been found. In the present invention, since the generated diphenylphosphoryl azide is present in the non-water-miscible solvent layer, a washing step with water can be performed, so that the hydrolyzate is removed and the substance causing coloring is removed. Therefore, a high-quality product having a high purity and a constant colorless liquid can be obtained.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, diphenylphosphoryl chloride as a raw material may be produced by any method, or a commercially available product may be used.

Specific examples of the inorganic azide salt represented by the general formula (2) include sodium, potassium, lithium,
Examples include alkali metal or alkaline earth metal azides such as calcium and magnesium, and sodium azide is industrially suitable.

The amount of the inorganic azide used is usually in the range of 1.0 to 3.0 mol, preferably 1.0 to 1.1 mol, as hydrogen azide, per mol of diphenylphosphoryl chloride.

The phase transfer catalyst useful for anion transfer used in the present invention includes quaternary such as tetra-n-butylammonium bromide, tetra-n-butylammonium chloride, trioctylmethylammonium chloride and benzyltriethylammonium chloride. Ammonium salts, but are not limited thereto.

The amount of the catalyst used is usually in the range of 0.01 to 0.05 weight, preferably in the range of 0.02 to 0.03 weight per 1 weight of diphenylphosphoryl chloride.

Examples of the non-water-miscible inert solvent include hydrocarbons such as hexane and cyclohexane, ethers such as ethyl ether and isopropyl ether, halogenated hydrocarbons such as methylene chloride and ethylene chloride, toluene and benzene. , Xylene, dichlorobenzene, and other aromatic hydrocarbons, preferably cyclohexane, toluene, benzene, and isopropyl ether, and particularly preferably cyclohexane, but are not limited thereto.

The amount of the above-mentioned solvent to be used is generally in the range of 1 to 5 volumes, preferably in the range of 2 to 3 volumes, per 1 volume of diphenylphosphoryl chloride.

The amount of water used for converting the inorganic azide salt into an aqueous solution is usually in the range of 0.5 to 2 volumes, preferably 1.0 to 1.5 volumes, per 1 volume of diphenylphosphoryl chloride.

The reaction temperature is usually in the range of 0 to 25 ° C., preferably in the range of 0 to 20 ° C., because the higher the temperature, the faster the hydrolysis of the starting diphenylphosphoryl chloride and the generated diphenylphosphoryl azide. is there.

As the reaction time increases, the hydrolysis of the starting material diphenylphosphoryl chloride and the generated diphenylphosphoryl azide is promoted.
The range is from 5 to 5 hours, preferably from 1 to 2 hours.

In the liquid separation after the reaction, the diphenylphosphoryl chloride as a raw material, the hydrolyzate of diphenylphosphoryl azide formed and sodium chloride as a by-product are dissolved in water, so that they are easily removed as an aqueous layer. The phase transfer catalyst in the organic layer is removed from the organic layer by washing the organic layer twice with water. Therefore, the obtained diphenylphosphoryl azide is of high quality with few impurities.

The organic layer containing diphenylphosphoryl azide can be easily dried with anhydrous magnesium sulfate, and diphenylphosphoryl azide can be isolated by filtering off magnesium sulfate and distilling off the solvent.

[0023]

The present invention will be described more specifically with reference to the following examples. The present invention is not limited to these examples.

Example 1 In a 5 L four-necked round-bottomed flask equipped with a mechanical overhead stirrer, 242 g (3.72 mol) of sodium azide dissolved in 1000 g of water, 20 g of tetra-n-butylammonium bromide and 2000 m of cyclohexane were added.
while maintaining the temperature at 25 ° C. or lower in a cold water bath,
Under stirring, 1000 g of diphenylphosphoryl chloride (7
75 ml, 3.72 mol) was added dropwise. The mixture was further stirred at 20 ° C. for about 1 hour to complete the reaction. After separating the two-phase mixture, the cyclohexane layer was washed twice with 600 ml of water,
It was dried with 100 g of anhydrous magnesium sulfate. After filtering off the desiccant, the cake was washed with 200 ml of cyclohexane. The dried cyclohexane solution was concentrated under reduced pressure using an evaporator at an oil bath temperature of 40 ° C. or lower to obtain 962 g of colorless liquid diphenylphosphoryl azide. The yield based on diphenylphosphoryl chloride was 94%. Purity 98.7%, specific gravity 1.29.

Example 2 952 g of colorless liquid diphenylphosphoryl azide was obtained in the same manner as in Example 1 except that toluene was used instead of cyclohexane. The yield based on diphenylphosphoryl chloride was 93%. Purity 99.4
%, Specific gravity 1.29.

[0026]

Industrial Applicability The present invention provides a novel method for producing diphenylphosphoryl azide used as a dehydrating condensing agent useful in the production of pharmaceuticals and the like. When the present invention is employed, high-quality diphenylphosphoryl azide can be produced while obtaining a safe and stable high yield. Therefore, the economic and industrial value is extremely large.

 ──────────────────────────────────────────────────続 き Continuing from the front page (72) Inventor Jun Mitsui 2900 Sone-machi, Takasago-shi, Hyogo Toyo Kasei Kogyo Co., Ltd.

Claims (5)

[Claims] 1. An aqueous solution of a diphenylphosphoryl chloride of the formula (1) and an inorganic azide salt represented by the general formula (2) in a water-immiscible solution in the presence of a phase transfer catalyst useful for anion transfer. A method for producing diphenylphosphoryl azide represented by the formula (3), wherein the reaction is carried out in an inert solvent. Embedded image (1) M (N ₃ ) n (2) (wherein, M is an alkali metal or an alkaline earth metal, and n is 1 or 2). (3) 2. The method according to claim 1, wherein the inorganic azide salt is sodium azide. 3. A phase transfer catalyst useful for anion transfer,
2. A quaternary ammonium salt.
Or the method of claim 2. 4. The method according to claim 3, wherein the quaternary ammonium salt is tri-n-alkylmethylammonium chloride or tri-n-alkylmethylammonium bromide. (Alkyl has 1 carbon atom
10 to 10. ) 5. The method according to claim 1, wherein the non-water-miscible inert solvent is selected from the group consisting of cyclohexane, toluene, benzene and isopropyl ether. .